Cyclotron-based production of ⁶⁸Ga, [⁶⁸Ga]GaCl₃, and [⁶⁸Ga]Ga-PSMA-11 from a liquid target

To optimize the direct production of ⁶⁸Ga on a cyclotron, via the ⁶⁸Zn(p,n)⁶⁸Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced ⁶⁸Ga, extraction of [⁶⁸Ga]GaCl₃ and subsequent [⁶⁸Ga]Ga-PSMA-11 labeling using an automated synthesis module.

Irradiations of a 1.0 M solution of [⁶⁸Zn]Zn(NO₃)₂ in dilute (0.2-0.3 M) HNO₃ were conducted using GE PETtrace cyclotrons and GE ⁶⁸Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of ⁶⁷Ga through the ⁶⁸Zn(p,2n)⁶⁷Ga reaction without unduly compromising ⁶⁸Ga yields. We also evaluated the effects of varying beam times (50-75 min) and beam currents (27-40 μA). Crude ⁶⁸Ga production was measured. The extraction of [⁶⁸Ga]GaCl₃ was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [⁶⁸Ga]GaCl₃ was used to label [⁶⁸Ga]Ga-PSMA-11 that was intended for clinical use.

The decay corrected yield of ⁶⁸Ga at EOB was typically > 3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [⁶⁸Zn]Zn(NO₃)₂ at 0.3 M HNO_3. Target/chemistry performance was more consistent when compared with 0.2 M HNO₃. Radionuclidic purity of ⁶⁸Ga was typically > 99.8% at EOB and met the requirements specified in the European Pharmacopoeia (< 2% combined ^66/67Ga) for a practical clinical product shelf-life. The activity yield of [⁶⁸Ga]GaCl₃ was typically > 50% (~ 1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [⁶⁸Ga]Ga-PSMA-11 were near quantitative (~ 1.67 GBq, 45 mCi) at EOS. Cyclotron produced [⁶⁸Ga]Ga-PSMA-11 underwent full quality control, stability and sterility testing, and was implemented for human use at the University of Michigan as an Investigational New Drug through the US FDA and also at the Royal Prince Alfred Hospital (RPA).

Direct cyclotron irradiation of a liquid target provides clinically relevant quantities of [⁶⁸Ga]Ga-PSMA-11 and is a viable alternative to traditional ⁶⁸Ge/⁶⁸Ga generators.